Daiichi Sankyo has offered up the freshest case study of just where the line is drawn on cancer drugs showing incremental — or even questionable — benefits, as critical internal reviews from the FDA translated into differing advisory committee opinions on two of its pitches.

By a 3-8 margin, the oncology experts convened by the agency shot down the Japanese drugmaker’s case for its acute myeloid leukemia drug quizartinib, having voted in favor of pexidartinib in the morning session. Pexidartinib treats benign tumors known as symptomatic tenosynovial giant cell tumor.

Designed specifically for FLT3-ITD–positive AML, quizartinib was heralded as a significant new option for refractory patients who are counting their last days. Daiichi Sankyo bagged the tyrosine kinase inhibitor in a buyout of Ambit Biosciences valued at $410 million in 2014. Last August, the company scored a breakthrough therapy designation for it on the back of pivotal data that showed a 27% overall survival rate compared to 20% in the chemotherapy arm.

Richard Pazdur

But adcomm members sided with FDA reviewers in worrying that the results, despite being statistically significant, had to do with imbalances between the drug and chemo cohorts. Compared to the chemo arm, the quizartinib group had a higher percentage of patients who went on to receive hematopoietic stem cell transplants, a lower number of non-treated cases, and fewer instances of incomplete OS data — all pointing toward a potential bias.

Richard Pazdur, the powerful director of the FDA’s Oncology Center of Excellence, chimed in at the meeting, saying he hasn’t come across a result like this in 20 years.

“While we are disappointed by the outcome of today’s ODAC vote, we will work closely with the FDA as it completes the review of our submission,” said Antoine Yver, Daiichi Sankyo’s global head of oncology R&D.

Antoine Yver

Regulators, who are not obliged to follow the adcomm’s advice but often do, will have until August 25 to decide after extending an earlier deadline to review more data. Daiichi Sankyo’s loss here could be Astellas’ and Novartis’ gain as they continue to carve out a place for Xospata and Rydapt, respectively.

It’s a sharp contrast with pexidartinib, which would be the first non-surgical treatment for a rare but often debilitating condition involving tumors in joints and tendons.

Here the main concern was liver toxicity, a concern that had previously curtailed enrollment in a Phase III. While adcomm members acknowledged the safety issues, the majority of them trusted a decent risk evaluation and mitigation strategy, or REMS, would sufficiently lower the risks.

Though the FDA also raised questions about efficacy, citing a “high level of missing data at Week 25,” 12 of the experts on the panel had no problem endorsing the benefits over the risks.

“I did not see the longitude in the data around 25 weeks and this is why I took more of the conservative side,” added one of the 3 who voted no. “I was worried about the efficacy and quality of life data beyond 25 weeks.”

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